Abstract：
:Carcinogenicity is an important toxicological endpoint that poses high concern to drug discovery. In this study, we developed a method to extract structural alerts (SAs) and modulating factors of carcinogens on the basis of statistical analyses. First, the Gaston algorithm, a frequent subgraph mining method, was used to detect substructures that occurred at least six times. Then, a molecular fragments tree was built and pruned to select high-quality SAs. The p-value of the parent node in the tree and that of its children nodes were compared, and the nodes that had a higher statistical significance in binomial tests were retained. Finally, modulating factors that suppressed the toxic effects of SAs were extracted by three self-defining rules. The accuracy of the 77 SAs plus four SA/modulating factor pairs model for the training set, and the test set was 0.70 and 0.65, respectively. Our model has higher predictive ability than Benigni's model, especially in the test set. The results highlight that this method is preferable in terms of prediction accuracy, and the selected SAs are useful for prediction as well as interpretation. Moreover, our method is convenient to users in that it can extract SAs from a database using an automated and unbiased manner that does not rely on a priori knowledge of mechanism of action.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Wang Y,Lu J,Wang F,Shen Q,Zheng M,Luo X,Zhu W,Jiang H,Chen Kdoi
10.1021/ci300266psubject
Has Abstractpub_date
2012-08-27 00:00:00pages
1994-2003issue
8eissn
1549-9596issn
1549-960Xjournal_volume
52pub_type
杂志文章abstract：:An index of the activation of Class A G-protein-coupled receptors (GPCRs) has been trained using interhelix distances from a series of microsecond molecular-dynamics simulations and tested for 268 published X-ray structures. In a three-class model that includes intermediate structures, 63% of the active structures are...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00604
更新日期：2019-09-23 00:00:00
abstract：:Small molecules targeting peripheral CB1 receptors have therapeutic potential in a variety of disorders including obesity-related, hormonal, and metabolic abnormalities, while avoiding the psychoactive effects in the central nervous system. We applied our in-house algorithm, iterative stochastic elimination, to produc...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
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更新日期：2019-09-23 00:00:00
abstract：:Target-oriented substructure-based virtual screening (sSBVS) of molecules is a promising approach in drug discovery. Yet, there are doubts whether sSBVS is suitable also for extrapolation, that is, for detecting molecules that are very different from those used for training. Herein, we evaluate the predictive power of...
journal_title：Journal of chemical information and modeling
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更新日期：2012-03-26 00:00:00
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journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.5b00514
更新日期：2015-12-28 00:00:00
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journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci050257m
更新日期：2005-11-01 00:00:00
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journal_title：Journal of chemical information and modeling
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更新日期：2020-07-27 00:00:00
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journal_title：Journal of chemical information and modeling
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更新日期：2017-06-26 00:00:00
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journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.7b00316
更新日期：2018-01-22 00:00:00
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journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci200617d
更新日期：2012-04-23 00:00:00
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journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.7b00347
更新日期：2017-09-25 00:00:00
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journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.7b00384
更新日期：2018-02-26 00:00:00
abstract：:Simulating protein flexibility is a major issue in the docking-based drug-design process for which a single methodological solution does not exist. In our search of new anti-Alzheimer ligands, we were faced with the challenge of including receptor plasticity in a virtual screening campaign aimed at finding new β-secre...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci300390h
更新日期：2012-10-22 00:00:00
abstract：:In this account, a rapid retrosynthesis-based scoring method for the assessment of synthetic accessibility of drug-like molecules, called RASA (Retrosynthesis-based Assessment of Synthetic Accessibility) is devised. RASA first constructs a synthesis tree for the target molecule based on retrosynthetic analysis; in thi...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci100216g
更新日期：2011-10-24 00:00:00
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journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci700026v
更新日期：2007-09-01 00:00:00
abstract：:The predictive performances of MC4PC were evaluated using its learning machine functionality. Its superior characteristics are demonstrated in this following up study using the newly published Ames mutagenicity benchmark set. ...
journal_title：Journal of chemical information and modeling
pub_type： 评论,信件
doi：10.1021/ci1000899
更新日期：2010-09-27 00:00:00
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journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci060073n
更新日期：2007-01-01 00:00:00
abstract：:Protein farnesyltransferase (FTase) is an important anticancer drug target. In an effort to develop isoprenoid diphosphate-based FTase inhibitors, striking variations have been observed in the ability of conservatively modified analogues to bind to the enzyme. For example, 2Z-GGPP is an alternative substrate with high...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci0496550
更新日期：2005-07-01 00:00:00
abstract：:Molecular docking can account for receptor flexibility by combining the docking score over multiple rigid receptor conformations, such as snapshots from a molecular dynamics simulation. Here, we evaluate a number of common snapshot selection strategies using a quality metric from stratified sampling, the efficiency of...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00314
更新日期：2018-09-24 00:00:00
abstract：:Sixteen FDA-approved drugs were investigated to elucidate their mechanisms of action (MOAs) and clinical functions by pathway analysis based on retrieved drug targets interacting with or affected by the investigated drugs. Protein and gene targets and associated pathways were obtained by data-mining of public database...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci4005354
更新日期：2014-02-24 00:00:00
abstract：:There are only four derivatives of pseudouridine (Ψ) that are known to occur naturally in RNA as post-transcriptional modifications. We have studied the conformational consequences of pseudouridylation and further modifications using replica exchange molecular dynamics simulations at the nucleoside level, and the simu...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.0c00369
更新日期：2020-10-26 00:00:00
abstract：:Sterol 14α-demethylase (CYP51) is the main drug target for the treatment of fungal infections. The discovery of new efficient fungal CYP51 inhibitors requires an understanding of the structural requirements for selectivity for the fungal over the human ortholog. In this study, a binding mode of the pyridylethanol(phen...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci500556k
更新日期：2014-12-22 00:00:00
abstract：:Identifying drug-target interactions (DTIs) plays an important role in the field of drug discovery, drug side-effects, and drug repositioning. However, in vivo or biochemical experimental methods for identifying new DTIs are extremely expensive and time-consuming. Recently, in silico or various computational methods h...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
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更新日期：2019-07-22 00:00:00
abstract：:LEAFY (LFY) is a plant-specific transcription factor, with a variety of roles in different species. LFY contains a conserved DNA-binding domain (DBD) that determines its DNA-binding specificity. Recently, the structures of the dimeric LFY-DBD bound to different DNA motifs were successively solved by X-ray crystallogra...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
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更新日期：2015-04-27 00:00:00
abstract：:Rotational Profiler provides an analytical algorithm to compute sets of classical torsional dihedral parameters by fitting an empirical energy profile to a reference one that can be obtained experimentally or by quantum-mechanical methods. The resulting profiles are compatible with the functional forms in the most wid...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.0c01168
更新日期：2020-12-28 00:00:00
abstract：:Ab initio quantum-chemistry programs produce and use large amounts of data, which are usually stored on disk in the form of binary files. A FORTRAN library, named Q5Cost, has been designed and implemented in order to allow the storage of these data sets in a special data format built with the HDF5 technology. This dat...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci7000567
更新日期：2007-05-01 00:00:00
abstract：:Umami or the taste of monosodium glutamate represents one of the major attractive taste modalities in humans. Therefore, knowledge about biophysical and biochemical properties of the umami taste is important for both scientific research and the food industry. Experimental approaches for predicting umami peptides are l...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.0c00707
更新日期：2020-12-28 00:00:00
abstract：:Engineered nanomaterials (ENMs) are increasingly infiltrating our lives as a result of their applications across multiple fields. However, ENM formulations may result in the modulation of pathways and mechanisms of toxic action that endanger human health and the environment. Alternative testing methods such as in sili...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.7b00223
更新日期：2017-09-25 00:00:00
abstract：:In a departure from conventional chemical approaches, data-driven models of chemical reactions have recently been shown to be statistically successful using machine learning. These models, however, are largely black box in character and have not provided the kind of chemical insights that historically advanced the fie...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00721
更新日期：2020-03-23 00:00:00
abstract：:The solvation layer surrounding a protein is clearly an intrinsic part of protein structure-dynamics-function, and our understanding of how the hydration dynamics influences protein function is emerging. We have recently reported simulations indicating a correlation between regional hydration dynamics and the structur...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00009
更新日期：2019-05-28 00:00:00
abstract：:Here, a method is described for easily building three-carbon nanotube junctions. It allows the geometry to be found and bond connectivity of C(3) symmetric nanotube junctions to be established. Such junctions may present a variable degree of pyramidalization and are composed of three identical carbon nanotubes with ar...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci200056p
更新日期：2011-06-27 00:00:00
